Benzodiazepines in Pain Practice: Necessary But Troubling

I have yet to find a pain practitioner who really likes prescribing benzodiazepines. In just about every guideline or protocol that involves prescribing opioids, there’s always an admonition to not mix opioids and benzodiazepines. No wonder. Practically every opioid overdose involves the addition of one or more benzodiazepines.

Don’t we wish we could avoid using this combination? No one likes to talk about it, but we all flinch and end up resorting to a benzodiazepine when the patient can’t sleep, even with melatonin or zolpidem (Ambien), or when muscles continue to spasm despite treatment with baclofen and tizanidine.

Despite all the warnings and a long search for non-benzodiazepine options, including antidepressants, neuropathic agents, muscle relaxants, and sedatives, the use of benzodiazepines as central nervous system sedatives/anxiolytics continues to increase among pain patients. A recent study presented at the American Academy of Pain Medicine annual meeting in Phoenix showed that simultaneous prescribing of benzodiazepines with opioids has increased by about 12% a year since 2002.1 Indeed, I can’t recall the last time a pain patient who wasn’t taking one or more benzodiazepines was referred to me.

It’s clear that benzodiazepine use among pain patients may be here for a while. But why pain patients flock to them is not clear. Benzodiazepines certainly have stood the test of time. Chlordiazepoxide (Librium) and diazepam (Valium) came onto the commercial market in the early 1960s. Today, I count at least 12 benzodiazepines in clinical use—alprazolam, chlordiazepoxide, clonazepam, clorazepate, diazepam, lorazepam, oxazepam and the prescription benzodiazepines that are FDA-approved for sleep disorders—estazolam, flurazepam, quazepam, temazepam, and triazolam.

The discovery of the benzodiazepine receptors gives us a clue as to their popularity. These compounds are believed to increase the efficiency of synaptic transmission of the neurotransmitter gamma-aminobutyric acid (GABA) by acting on its receptors. Benzodiazepines bind to a specific site on the GABA-benzodiazepine receptor complex.

Some authors have postulated why benzodiazepines are so popular with pain patients. Anxiety may increase the unpleasantness of pain or it may increase muscle tension and sympathetic outflow.2 I personally believe the hyperarousal of the autonomic, sympathetic nervous system that occurs with centralization of pain and central sensitization is a major factor in pain patients’ desire to use benzodiazepines. With sympathetic hyperarousal, patients often describe a feeling of tremor, “coming unglued,” inability to concentrate, migratory pain movements, and insomnia. All in all, patients describe a dysphoric feeling that responds well only to benzodiazepines.

The dosage of benzodiazepine that some pain patients can take and remain functioning is remarkable. Patients may carry a blood level of benzodiazepines of several hundred nanograms per mL and not be sedated. The message here is that some patients become extremely tolerant to the sedative effect of benzodiazepines and function well at a very high dosage, even while simultaneously using opioids.

Where Do We Go From Here?

First, there must be general recognition that the hyperarousal of the autonomic sympathetic nervous system in some centralized pain patients is so severe that patients will repeatedly ask to be treated with benzodiazepines because these agents have helped to manage their symptoms in the past. In other cases, after assessing the patient, the physician may suggest adding a benzodiazepine. Physicians should make chart entries that describe the appearance, alertness, and level of functioning of patients prescribed benzodiazepines. Because benzodiazepines can be abused, it is standard of care to have patients undergo urine drug testing, which patients on opioids should be undergoing randomly a couple of times a year, plus whenever there is an issue. A blood test to establish blood levels can be done to document, in cases of high dosages, that he/she is tolerant to the sedative effect of a benzodiazepine.

Perhaps the best thing we can do is to stop sweeping this issue under the carpet. Let’s just accept the fact that benzodiazepines have been around for a long time and are apparently beneficial to the welfare and pain relief of many patients—improved sleep, less stress/anxiety, etc. It is critical that physicians counsel their patients on the proper management of their medications to avoid problems with the combination of medications, for example oversedation and respiratory depression. Rather than condemn benzodiazepines, what’s needed is some practical protocols and guidelines on how to use them safely and more effectively.

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